The Diabetes Prevention Program is a randomized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk persons with elevated fasting plasma glucose concentrations and impaired glucose tolerance. The 27 clinical centers in the U.S.A. are recruiting participants consisting of approximately 50% minorities, 20% 65 years old, and both sexes, to be assigned at random to one of three intervention groups. Eligible volunteers were randomized to 3 intervention groups: an intensive lifestyle intervention focusing on a healthy diet and exercise, and 2 masked medication treatment groups - metformin, or placebo - combined with standard diet and exercise recommendations. The study design includes 1,000 participants in each of the three treatment groups. Participants are being recruited during a 2.7 year period, and all will be followed for an additional 3.3 to 6 years after the close of recruitment to a common closing date in 2002. The primary outcome is the development of diabetes, diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria. The 3,000 participants will provide 90% power to detect a 33% reduction in an expected diabetes incidence rate of 6.5% per year in the placebo group. Secondary outcomes include cardiovascular disease and its risk factors; changes in glycemia, beta-cell function, insulin sensitivity, obesity, diet, physical activity, and health-related quality of life; and occurrence of adverse events. A randomized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in persons at high risk.